Primary biliary cirrhosis shows association with genetic polymorphism of tumour necrosis factor alpha promoter region
Primary biliary cirrhosis shows association with genetic polymorphism of tumour necrosis factor alpha promoter region
复制标题
DOI：
10.1016/s0168-8278(99)80220-7
复制
发表时间：
1999-08-01
影响因子：
25.7
通讯作者：
Gleeson, D
中科院分区：
文献类型：
--
作者：
Gordon, MA;Oppenheim, E;Gleeson, D
背景/目的：原发性胆汁性肝硬变是一种自身免疫性疾病，其一级亲属的患病率增加，与人类白细胞抗原DR8的相关性提示有遗传背景，肿瘤坏死因子α是炎症和免疫的介质，并与原发性胆汁性肝硬变的发病机制有关，体外研究表明患者淋巴细胞产生的肿瘤坏死因子α减少。本课题组先前已报道了TNFA基因-308位点的双等位基因启动子区多态性，并证明了罕见的等位基因TNF*2比常见的等位基因TNF*1具有更强的启动子功能。进一步的双等位碱基改变被描述在-238位，我们进行了一项病例对照研究，以评估这些基因多态与原发性胆汁性肝硬变的关系。聚合酶链式反应产物的限制性片段长度多态性分析。结果：高表达的TNFA-308*2等位基因在原发性胆汁性肝硬化组中显著低于对照组(27.5%PBC，41.6%，P=0.02，PC=0.04，携带肿瘤坏死因子*1/*1的OR=1.89，CI=1.10~3.32)。结论：原发性胆汁性肝硬变与肿瘤坏死因子2的携带减少有关，这与肿瘤坏死因子α对疾病的保护作用是一致的。
Background/Aims: Primary biliary cirrhosis is an autoimmune disease in which increased prevalence in first-degree relatives and an association with HLA DR8 suggest a genetic background, TNF alpha is a mediator of inflammation and immunity, and is implicated in the pathogenesis of primary biliary cirrhosis, ex vivo studies having shown reduced production of TNF alpha by lymphocytes from patients. Our group has previously described a biallelic promoter-region polymorphism of the TNFA gene at position -308, and demonstrated that the rare allele, TNF*2, has increased promoter function compared with the common allele, TNF*1. A further biallelic base change has been described in the TNFA gene at -238, We conducted a case-control study to assess association of these gene polymorphisms with primary biliary cirrhosis.Methods: Ninety-one patients and 213 controls were genotyped for both TNFA loci using. restriction fragment length polymorphism analysis of PCR products. Results: The high production TNFA-308*2 allele was significantly under-represented among subjects with primary biliary cirrhosis (27.5% PBC, 41.6% controls, p=0.02, pc=0.04, OR for carriage of TNF*1/*1 genotype=1.89, CI=1.10-3.32). No association was shown with the TNFA -238 polymorphism.Conclusion: Primary biliary cirrhosis is associated with reduced carriage of TNF*2, This is in keeping with a protective role of TNF alpha against the disease.